Figure 1.

The mechanisms of fertilization, elucidated by gene-manipulated animals. (a) Spermatozoa that present Adam3 (or some unknown factor(s)) can migrate into the oviduct and reach the vicinity of the eggs. Acrosome reaction is induced before spermatozoa reach the zona pellucida and the fusion-related sperm protein Izumo1 on the outer acrosomal membrane migrates out to sperm surface (indicated by red color). (b) Spermatozoa bind to zona pellucida when mixed with cumulus-free oocytes.74 However, this binding (mostly observed between the acrosome-intact spermatozoa and zona pellucida) was dispensable. The spermatozoa that lost the so-called “zona-binding” ability remained able to fertilize eggs in vivo once the oviduct migration step was bypassed.29,31,33 Moreover, the timing of the acrosome reaction is flexible, as acrosome-reacted spermatozoa recovered from the perivitelline space could penetrate the zona pellucida a second time and fertilize eggs.43 The mechanism of sperm penetration of zona pellucida is largely unknown. (c) Only acrosome-reacted spermatozoa can fuse with eggs. Spermatozoa without Izumo1 never fused with eggs.39 Cd9 on the egg played an important role in fertilization,40,41,42 but Cd9-disrupted females were not completely infertile. In addition, no direct interaction between Cd9 and Izumo1 was observed. This led us to predict a real counterpart for Izumo1. Using the newly established AVEXIS assay, JUNO was recently found to be a counterpart for Izumo1 on the egg.51 Modified from review.75